Prolonged fasting or clonidine can restore the defective growth hormone secretion in old dogs

Age-related changes in GH secretion were studied in dog. In preliminary experiments, administration of GH-releasing hormone (GHRH-40, 2 micrograms/kg, iv) or the alpha 2-adrenoceptor agonist clonidine (4 micrograms/kg, iv) elicited significantly higher plasma GH rises in 3 to 4 years old than in 10 to 14 years old beagle dogs. The pulsatile patterns of GH secretion in both young and old dogs under baseline conditions and after prolonged fasting or clonidine administration were studied. Samples were taken every 10 min from 09.00 to 15.00 h from five young and five old dogs of both sexes. Under baseline conditions, GH peak frequency, total peak area, and integrated GH secretion were significantly lower in old than in young dogs. In old dogs, 5-day complete fasting or 14-day clonidine administration (75 micrograms/dog, po, twice daily) increased the frequency and amplitude of spontaneous GH bursts, the total peak area, and the integrated GH secretion. After either stimulus, the GH secretory pattern was quantitatively and qualitatively indistinguishable from that of young dogs under baseline conditions. Similarly, the foregoing indices were significantly increased in young dogs by either stimulus, except for the inability of clonidine to affect peak frequency. These data demonstrate that the defective GH secretion in old dogs is not irreversible, since it is normalized when old dogs are exposed to central nervous system-directed stimuli.